title: Clinical features of three girls with mosaic genome-wide paternal uniparental isodisomy.
abstract: Here we describe three subjects with mosaic genome-wide paternal uniparental isodisomy (GWpUPD) each of whom presented initially with overgrowth, hemihyperplasia (HH), and hyperinsulinism (HI). Due to the severity of findings and the presence of additional features, SNP array testing was performed, which demonstrated mosaic GWpUPD. Comparing these individuals to 10 other live-born subjects reported in the literature, the predominant phenotype is that of pUPD11 and notable for a very high incidence of tumor development. Our subjects developed non-metastatic tumors of the adrenal gland, kidney, and/or liver. All three subjects had pancreatic hyperplasia resulting in HI. Notably, our subjects to date display minimal features of other diseases associated with paternal UPD loci. Both children who survived the neonatal period have displayed near-normal cognitive development, likely due to a favorable tissue distribution of the mosaicism. To understand the range of UPD mosaicism levels, we studied multiple tissues using SNP array analysis and detected levels of 5-95%, roughly correlating with the extent of tissue involvement. Given the rapidity of tumor growth and the difficulty distinguishing malignant and benign tumors in these GWpUPD subjects, we have utilized increased frequency of ultrasound (US) and alpha-fetoprotein (AFP) screening in the first years of life. Because of a later age of onset of additional tumors, continued tumor surveillance into adolescence may need to be considered in these rare patients.
authors.affiliation: The Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kalish
authors.forename: Laura K
authors.initials: LK
authors.lastname: Conlin
authors.forename: Tricia R
authors.initials: TR
authors.lastname: Bhatti
authors.forename: Holly A
authors.initials: HA
authors.lastname: Dubbs
authors.forename: Mary Catherine
authors.initials: MC
authors.lastname: Harris
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Sogol
authors.initials: S
authors.lastname: Mostoufi-Moab
authors.forename: Surabhi
authors.initials: S
authors.lastname: Mulchandani
authors.forename: Sulagna
authors.initials: S
authors.lastname: Saitta
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: States
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Swarr
authors.forename: Alisha B
authors.initials: AB
authors.lastname: Wilkens
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Kristin
authors.initials: K
authors.lastname: Zelley
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Bartolomei
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Palladino
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000235:genetics* / Q000473:pathology; D006946:Hyperinsulinism / Q000235:genetics* / Q000473:pathology; D006965:Hyperplasia / Q000235:genetics* / Q000473:pathology; D007223:Infant; D008279:Magnetic Resonance Imaging; D009030:Mosaicism; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D024182:Uniparental Disomy / Q000235:genetics* / Q000473:pathology; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000509:alpha-Fetoproteins
keywords: Beckwith-Wiedemann; hyperinsulinism; isodisomy; methylation; mosaicism; uniparental disomy